The fate of digoxin in human subjects is being studied by radioimmunoassay, by the use of 3H-digoxin and by gas-liquid and thin-layer chromatography. Studies on the content of digoxin in the human heart by biopsy at the time of cardiac surgery have been followed by related studies in dogs. In the studies on dogs that are now being carried out, the amount of digoxin in the heart and other organs is being determined by biopsy at the same time the blood concentration of drug is assayed. In addition to the work described, we are exploring the use of gas-liquid chromatography combined with mass spectrometry to study the metabolic products of digoxin in man.